Bagatto Brian, Francl Jessie, Liu Bei, Liu Qin
Department of Biology, University of Akron, Akron, Ohio, USA.
BMC Dev Biol. 2006 May 23;6:23. doi: 10.1186/1471-213X-6-23.
Cadherins are cell surface adhesion molecules that play important roles in development of vertebrate tissues and organs. We studied cadherin2 expression in developing zebrafish heart using in situ hybridization and immunocytochemical methods, and we found that cadherin2 was strongly expressed by the myocardium of the embryonic zebrafish. To gain insight into cadherin2 role in the formation and function of the heart, we analyzed cardiac differentiation and performance in a cadherin2 mutant, glass onion (glo).
We found that the cadherin2 mutant had enlarged pericardial cavity, disorganized atrium and ventricle, and reduced expression of a ventricular specific marker vmhc. Individual myocardiocytes in the glo mutant embryos became round shaped and loosely aggregated. In vivo measurements of cardiac performance revealed that the mutant heart had significantly reduced heart rate, stroke volume and cardiac output compared to control embryos. Formation of the embryonic vascular system in the glo mutants was also affected.
Our results suggest that cadherin2 plays an essential role in zebrafish cardiovascular development. Although the exact mechanisms remain unknown as to the formation of the enlarged pericardium and reduced peripheral blood flow, it is clear that myocardiocyte differentiation and physiological cardiovascular performance is impaired when cadherin2 function is disrupted.
钙黏着蛋白是细胞表面黏附分子,在脊椎动物组织和器官发育中发挥重要作用。我们使用原位杂交和免疫细胞化学方法研究了发育中的斑马鱼心脏中钙黏着蛋白2的表达,发现胚胎斑马鱼的心肌强烈表达钙黏着蛋白2。为深入了解钙黏着蛋白2在心脏形成和功能中的作用,我们分析了钙黏着蛋白2突变体玻璃洋葱(glo)中的心脏分化和功能表现。
我们发现钙黏着蛋白2突变体的心包腔扩大,心房和心室结构紊乱,心室特异性标志物vmhc的表达降低。glo突变体胚胎中的单个心肌细胞变成圆形并松散聚集。对心脏功能表现的体内测量显示,与对照胚胎相比,突变体心脏的心率、每搏输出量和心输出量显著降低。glo突变体中胚胎血管系统的形成也受到影响。
我们的结果表明钙黏着蛋白2在斑马鱼心血管发育中起重要作用。尽管心包扩大和外周血流减少的确切形成机制尚不清楚,但很明显,当钙黏着蛋白2功能被破坏时,心肌细胞分化和生理性心血管功能表现会受损。